tbuckley/cabot-search huggingface dataset:
Prevention and Initial Management of HIV Infection
Authors: Judith Feinberg, Susana Keeshin
Journal: Annals of Internal Medicine (2022)

LettersDecember 2022Prevention and Initial Management of HIV InfectionJudith Feinberg, MD, Susana Keeshin, MDJudith Feinberg, MDWest Virginia University School of Medicine, Morgantown, West VirginiaSearch for more papers by this author, Susana Keeshin, MDUniversity of Utah School of Medicine, Salt Lake City, UtahSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L22-0395 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: We thank Dr. Wei and colleagues for raising concerns about HIV transmission among migrating populations who may be at high risk for HIV infection. It is important that countries where migrants finally settle screen for HIV as well as for other infectious diseases—such as tuberculosis—that are frequently seen in these populations. Author, Article, and Disclosure InformationAffiliations: West Virginia University School of Medicine, Morgantown, West VirginiaUniversity of Utah School of Medicine, Salt Lake City, UtahDisclosures: Dr. Feinberg, ACP Contributing Author, reports a research contract from Gilead Sciences, consulting fees from Gilead Sciences and ViiV Healthcare, payment for expert testimony from Motley Rice LLC, and leadership roles in the HIV Medicine Association. Dr. Keeshin, ACP Contributing Author, reports no disclosures of interest. All relevant financial relationships have been mitigated. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-0039. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPrevention and Initial Management of HIV Infection Yongbao Wei , Ruochen Zhang , Tao Li , Liefu Ye , and Le Lin Metrics December 2022Volume 175, Issue 12Page: W152KeywordsAntiretroviral therapyDrugsHIVHIV infectionsHIV preventionOpportunistic infectionsPreexposure prophylaxisPregnancyViral load ePublished: 20 December 2022 Issue Published: December 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape
Authors: Mahdi Golkaram, Fengshen Kuo, Sounak Gupta, Maria I. Carlo, Michael L. Salmans, Raakhee Vijayaraghavan, Cerise Tang, Vlad Makarov, Phillip Rappold, Kyle A. Blum, Chen Zhao, Rami Mehio, Shile Zhang, Jim Godsey, Traci Pawlowski, Renzo G. DiNatale, Luc G. T. Morris, Jeremy Durack, Paul Russo, Ritesh R. Kotecha, Jonathan Coleman, Ying-Bei Chen, Victor E. Reuter, Robert J. Motzer, Martin H. Voss, Li Liu, Ed Reznik, Timothy A. Chan, A. Ari Hakimi
Journal: Genome Medicine (2022)

Abstract Background Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance. Methods Here, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC. Primary endpoints were safety and feasibility of neoadjuvant nivolumab. Then, we spatiotemporally profiled the genomic and immunophenotypic characteristics of 29 ccRCC patients, including pre- and post-therapy samples from 17 ICI-treated patients. Deep multi-regional whole-exome and transcriptome sequencing were performed on 29 patients at different time points before and after ICI therapy. T cell repertoire was also monitored from tissue and peripheral blood collected from a subset of patients to study T cell clonal expansion during ICI therapy. Results Angiogenesis, lymphocytic infiltration, and myeloid infiltration varied significantly across regions of the same patient, potentially confounding their utility as biomarkers of ICI response. Elevated ITH associated with a constellation of both genomic features (HLA LOH, CDKN2A/B loss) and microenvironmental features, including elevated myeloid expression, reduced peripheral T cell receptor (TCR) diversity, and putative neoantigen depletion. Hypothesizing that ITH may itself play a role in shaping ICI response, we derived a transcriptomic signature associated with neoantigen depletion that strongly associated with response to ICI and targeted therapy treatment in several independent clinical trial cohorts. Conclusions These results argue that genetic and immune heterogeneity jointly co-evolve and influence response to ICI in ccRCC. Our findings have implications for future biomarker development for ICI response across ccRCC and other solid tumors and highlight important features of tumor evolution under ICI treatment. Trial registration The study was registered on ClinicalTrial.gov (NCT02595918) on November 4, 2015.
Socially transferred materials: why and how to study them
Authors: Sanja Maria Hakala, Haruna Fujioka, Katharina Gapp, Ornela De Gasperin, Eléonore Genzoni, Rebecca M. Kilner, Joris M. Koene, Barbara König, Timothy A. Linksvayer, Marie-Pierre Meurville, Matteo A. Negroni, Hugo Palejowski, Stuart Wigby, Adria C. LeBoeuf
Journal: Trends in Ecology & Evolution (2022)

When biological material is transferred from one individual's body to another, as in ejaculate, eggs, and milk, secondary donor-produced molecules are often transferred along with the main cargo, and influence the physiology and fitness of the receiver. Both social and solitary animals exhibit such social transfers at certain life stages. The secondary, bioactive, and transfer-supporting components in socially transferred materials have evolved convergently to the point where they are used in applications across taxa and type of transfer. The composition of these materials is typically highly dynamic and context dependent, and their components drive the physiological and behavioral evolution of many taxa. Our establishment of the concept of socially transferred materials unifies this multidisciplinary topic and will benefit both theory and applications.
Mapping the T cell epitopes of the M-type transmembrane phospholipase A2 receptor in primary membranous nephropathy
Authors: Xiao-dan Zhang, Cai-xia Lin, Zhao Cui, Qiu-hua Gu, Bing-jia Yan, Lei Liu, Wen-chao Song, Yi Shi, Hanna Debiec, Pierre Ronco, Ming-hui Zhao
Journal: Kidney International (2022)
Impact of systemic therapies in metastatic melanoma of unknown primary: A study from MELBASE, a French multicentric prospective cohort
Authors: Perrine Rousset, Stéphane Dalle, Laurent Mortier, Olivier Dereure, Sophie Dalac, Caroline Dutriaux, Marie-Thérèse Leccia, Delphine Legoupil, Florence Brunet-Possenti, Julie De Quatrebarbes, Jean-Jacques Grob, Philippe Saiag, Eve Maubec, Pierre-Emmanuel Stoebner, Florence Granel-Brocard, Jean-Philippe Arnault, Clara Allayous, Bastien Oriano, Céleste Lebbe, Henri Montaudié
Journal: Journal of the American Academy of Dermatology (2022)
Innate immune signaling drives late cardiac toxicity following DNA-damaging cancer therapies
Authors: Achraf Shamseddine, Suchit H. Patel, Valery Chavez, Zachary R. Moore, Mutayyaba Adnan, Melody Di Bona, Jun Li, Chau T. Dang, Lakshmi V. Ramanathan, Kevin C. Oeffinger, Jennifer E. Liu, Richard M. Steingart, Alessandra Piersigilli, Nicholas D. Socci, Angel T. Chan, Anthony F. Yu, Samuel F. Bakhoum, Adam M. Schmitt
Journal: The Journal of Experimental Medicine (2022)

Late cardiac toxicity is a potentially lethal complication of cancer therapy, yet the pathogenic mechanism remains largely unknown, and few treatment options exist. Here we report DNA-damaging agents such as radiation and anthracycline chemotherapies inducing delayed cardiac inflammation following therapy due to activation of cGAS- and STING-dependent type I interferon signaling. Genetic ablation of cGAS–STING signaling in mice inhibits DNA damage–induced cardiac inflammation, rescues late cardiac functional decline, and prevents death from cardiac events. Treatment with a STING antagonist suppresses cardiac interferon signaling following DNA-damaging therapies and effectively mitigates cardiac toxicity. These results identify a therapeutically targetable, pathogenic mechanism for one of the most vexing treatment-related toxicities in cancer survivors.
Neurocognitive, physiological, and biophysical effects of transcranial alternating current stimulation
Authors: Miles Wischnewski, Ivan Alekseichuk, Alexander Opitz
Journal: Trends in Cognitive Sciences (2022)

Transcranial alternating current stimulation (tACS) can modulate human neural activity and behavior. Accordingly, tACS has vast potential for cognitive research and brain disorder therapies. The stimulation generates oscillating electric fields in the brain that can bias neural spike timing, causing changes in local neural oscillatory power and cross-frequency and cross-area coherence. tACS affects cognitive performance by modulating underlying single or nested brain rhythms, local or distal synchronization, and metabolic activity. Clinically, stimulation tailored to abnormal neural oscillations shows promising results in alleviating psychiatric and neurological symptoms. We summarize the findings of tACS mechanisms, its use for cognitive applications, and novel developments for personalized stimulation.
Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior
Authors: Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes de Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R. Cox, Julia M. Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A. Scarcelli, Zili Yan, Kristine M. Conde, Camille Potts, Jonathan C. Bean, Mengjie Wang, Sean M. Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I. Sadaf Farooqi
Journal: Nature Medicine (2022)

Abstract Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT 2C R) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT 2C R ( HTR2C ) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Using the 5-HT 2C R agonist lorcaserin, we found that depolarization of appetite-suppressing proopiomelanocortin neurons was impaired in knock-in mice. In conclusion, we demonstrate that 5-HT 2C R is involved in the regulation of human appetite, weight and behavior. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying HTR2C variants. We suggest that HTR2C should be included in diagnostic gene panels for severe childhood-onset obesity.
Construction of multifunctional hydrogel with metal-polyphenol capsules for infected full-thickness skin wound healing
Authors: Nanbo Liu, Shuoji Zhu, Yuzhi Deng, Ming Xie, Mingyi Zhao, Tucheng Sun, Changjiang Yu, Ying Zhong, Rui Guo, Keluo Cheng, Dehua Chang, Ping Zhu
Journal: Bioactive Materials (2022)

Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds or even severe tissue damage. In this study, we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate (Cu-EGCG) nano-capsules. The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). It could also promote the proliferation and migration of L929 fibroblasts. In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect. Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group. The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.
Prognostic score and sex-specific nomograms to predict survival in resectable lung cancer: a French nationwide study from the Epithor cohort database
Authors: Marco Alifano, Elisa Daffré, Laurent Brouchet, Pierre Emmanuel Falcoz, Françoise Le Pimpec Barthes, Pierre Benoit Pages, Pascal Alexandre Thomas, Marcel Dahan, Raphael Porcher
Journal: The Lancet Regional Health - Europe (2022)

Prognostic assessment in patients undergoing cancer treatments is of paramount importance to plan subsequent management. In resectable lung cancer availability of an easy-to use nomogram to predict long-term outcome would be extremely useful to identify high-risk patients in the era of perioperative targeted and immune therapies.We retrieved clinical, surgical and pathological data of all consecutive patients included in Epithor, the database of French Society of Thoracic and Cardiovascular Surgery, and operated on between 2003 and 2020 for non-small cell lung cancer in a curative intent. The primary endpoint was overall survival up to 5 years. We assessed prognostic significance of available variables using Cox modelling, in the whole dataset, and in men and in women separately, and performed temporal validation. Finally, we constructed two sex-specific nomograms. Survivals by fifths of score were assessed in the development and temporal validation sets.The study included 62,633 patients (43,551 men and 19,082 women). Median survival time was 9.2 years. Nine factors had strong prognostic impact and were used to construct nomograms. The optimism-corrected c statistic for the prognostic score was 0.689 in the development sample, and 0.726 (95% CI 0.718-0.735) in the temporal validation sample. All differences between adjacent fifths of score were significant (P < 0.0001). Figures of 3-year OS by fifths of score were 92.2%, 83.0%, 74.3%, 64.0%, and 43.4%, respectively, in the development set and 93.3%, 88.4%, 81.0%, 73.7%, 55.7% in the temporal validation set. Performance of score was maintained when stratifying by stage of diseases.In the present work, we report evidence that long-term overall survival after resection of NSCLC can be predicted by an easy to construct and use composite score taking into account both host and tumour related factors.Epithor is funded by FSTCVS.
HYDI-DSI revisited: Constrained non-parametric EAP imaging without q-space re-gridding
Authors: Antonio Tristán-Vega, Tomasz Pieciak, Guillem París, Justino R Rodríguez-Galván, Santiago Aja-Fernández
Journal: Medical Image Analysis (2022)

Hybrid Diffusion Imaging (HYDI) was one of the first attempts to use multi-shell samplings of the q-space to infer diffusion properties beyond Diffusion Tensor Imaging (DTI) or High Angular Resolution Diffusion Imaging (HARDI). HYDI was intended as a flexible protocol embedding both DTI (for lower b-values) and HARDI (for higher b-values) processing, as well as Diffusion Spectrum Imaging (DSI) when the entire data set was exploited. In the latter case, the spherical sampling of the q-space is re-gridded by interpolation to a Cartesian lattice whose extent covers the range of acquired b-values, hence being acquisition-dependent. The Discrete Fourier Transform (DFT) is afterwards used to compute the corresponding Cartesian sampling of the Ensemble Average Propagator (EAP) in an entirely non-parametric way. From this lattice, diffusion markers such as the Return To Origin Probability (RTOP) or the Mean Squared Displacement (MSD) can be numerically estimated. We aim at re-formulating this scheme by means of a Fourier Transform encoding matrix that eliminates the need for q-space re-gridding at the same time it preserves the non-parametric nature of HYDI-DSI. The encoding matrix is adaptively designed at each voxel according to the underlying DTI approximation, so that an optimal sampling of the EAP can be pursued without being conditioned by the particular acquisition protocol. The estimation of the EAP is afterwards carried out as a regularized Quadratic Programming (QP) problem, which allows to impose positivity constraints that cannot be trivially embedded within the conventional HYDI-DSI. We demonstrate that the definition of the encoding matrix in the adaptive space allows to analytically (as opposed to numerically) compute several popular descriptors of diffusion with the unique source of error being the cropping of high frequency harmonics in the Fourier analysis of the attenuation signal. They include not only RTOP and MSD, but also Return to Axis/Plane Probabilities (RTAP/RTPP), which are defined in terms of specific spatial directions and are not available with the former HYDI-DSI. We report extensive experiments that suggest the benefits of our proposal in terms of accuracy, robustness and computational efficiency, especially when only standard, non-dedicated q-space samplings are available.
TIST: Transcriptome and Histopathological Image Integrative Analysis for Spatial Transcriptomics
Authors: Yiran Shan, Qian Zhang, Wenbo Guo, Yanhong Wu, Yuxin Miao, Hongyi Xin, Qiuyu Lian, Jin Gu
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Sequencing-based spatial transcriptomics (ST) is an emerging technology to study in situ gene expression patterns at the whole-genome scale. Currently, ST data analysis is still complicated by high technical noises and low resolution. In addition to the transcriptomic data, matched histopathological images are usually generated for the same tissue sample along the ST experiment. The matched high-resolution histopathological images provide complementary cellular phenotypical information, providing an opportunity to mitigate the noises in ST data. We present a novel ST data analysis method called transcriptome and histopathological image integrative analysis for ST (TIST), which enables the identification of spatial clusters (SCs) and the enhancement of spatial gene expression patterns by integrative analysis of matched transcriptomic data and images. TIST devises a histopathological feature extraction method based on Markov random field (MRF) to learn the cellular features from histopathological images, and integrates them with the transcriptomic data and location information as a network, termed TIST-net. Based on TIST-net, SCs are identified by a random walk-based strategy, and gene expression patterns are enhanced by neighborhood smoothing. We benchmark TIST on both simulated datasets and 32 real samples against several state-of-the-art methods. Results show that TIST is robust to technical noises on multiple analysis tasks for sequencing-based ST data and can find interesting microstructures in different biological scenarios. TIST is available at http://lifeome.net/software/tist/ and https://ngdc.cncb.ac.cn/biocode/tools/BT007317.
Superior Fidelity and Distinct Editing Outcomes of SaCas9 Compared with SpCas9 in Genome Editing
Authors: Zhi-Xue Yang, Ya-Wen Fu, Juan-Juan Zhao, Feng Zhang, Si-Ang Li, Mei Zhao, Wei Wen, Lei Zhang, Tao Cheng, Jian-Ping Zhang, Xiao-Bing Zhang
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract A series of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9) systems have been engineered for genome editing. The most widely used Cas9 is SpCas9 from Streptococcus pyogenes and SaCas9 from Staphylococcus aureus. However, a comparison of their detailed gene editing outcomes is still lacking. By characterizing the editing outcomes of 11 sites in human induced pluripotent stem cells (iPSCs) and K562 cells, we found that SaCas9 could edit the genome with greater efficiencies than SpCas9. We also compared the effects of spacer lengths of single-guide RNAs (sgRNAs; 18–21 nt for SpCas9 and 19–23 nt for SaCas9) and found that the optimal spacer lengths were 20 nt and 21 nt for SpCas9 and SaCas9, respectively. However, the optimal spacer length for a particular sgRNA was 18–21 nt for SpCas9 and 21–22 nt for SaCas9. Furthermore, SpCas9 exhibited a more substantial bias than SaCas9 for nonhomologous end–joining (NHEJ) +1 insertion at the fourth nucleotide upstream of the protospacer adjacent motif (PAM), indicating a characteristic of a staggered cut. Accordingly, editing with SaCas9 led to higher efficiencies of NHEJ-mediated double-stranded oligodeoxynucleotide (dsODN) insertion or homology-directed repair (HDR)-mediated adeno-associated virus serotype 6 (AAV6) donor knock-in. Finally, GUIDE-seq analysis revealed that SaCas9 exhibited significantly reduced off-target effects compared with SpCas9. Our work indicates the superior performance of SaCas9 to SpCas9 in transgene integration-based therapeutic gene editing and the necessity to identify the optimal spacer length to achieve desired editing results.
Risk Factors for Metachronous Colorectal Cancer or Advanced Adenomas After Endoscopic Resection of High-risk Adenomas
Authors: Sandra Baile-Maxía, Carolina Mangas-Sanjuán, Uri Ladabaum, Cesare Hassan, Matthew D. Rutter, Michael Bretthauer, Lucía Medina-Prado, Noelia Sala-Miquel, Oscar Murcia Pomares, Pedro Zapater, Rodrigo Jover
Journal: Clinical Gastroenterology and Hepatology (2022)
Deaths from alcohol-related liver disease in the UK: an escalating tragedy
Authors: Michael E D Allison, Julia Verne, William Bernal, Michelle Clayton, Sam Cox, Ashwin Dhanda, John F Dillon, James Ferguson, Graham Foster, Ian Gilmore, Vanessa Hebditch, Rebecca Jones, Steven Masson, Beverley Oates, Paul Richardson, Julia Sinclair, Julia Wendon, David Wood
Journal: The Lancet (2022)
Pre-referral rectal artesunate: no cure for unhealthy systems
Authors: Manuel W Hetzel, Phyllis Awor, Antoinette Tshefu, Elizabeth Omoluabi, Christian Burri, Aita Signorell, Mark J Lambiris, Theodoor Visser, Justin M Cohen, Valentina Buj, Christian Lengeler
Journal: The Lancet Infectious Diseases (2022)
An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study
Authors: Emma Guttman-Yassky, Eric L Simpson, Kristian Reich, Kenji Kabashima, Ken Igawa, Tetsuya Suzuki, Hirotaka Mano, Takeshi Matsui, Ehsanollah Esfandiari, Masutaka Furue
Journal: The Lancet (2022)
Focused Empiricism and the Efficacy of Resuscitative Endovascular Balloon Occlusion of the Aorta
Authors: Todd E. Rasmussen
Journal: JAMA Surgery (2022)

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